Recent Advances in Palladium‐Catalyzed Cross‐Coupling Reactions at ppm to ppb Molar Catalyst Loadings

Abstract We review here new developments in decreasing the catalyst loadings in palladium‐catalyzed C–C bond‐formation reactions to mol ppm or mol ppb levels. This decreases the cost of the catalyst and the toxicity of the reaction system, making the reaction more attractive to industry. The Heck reaction, Sonogashira reaction, Suzuki–Miyaura cross‐coupling reaction, other cross‐coupling reactions, and allylic arylation reactions are separately discussed to show clearly the progress made in each type of reaction. Apart from the catalyst loading, the other parameters of the reaction (temperature, solvent, etc.) are briefly discussed to illustrate the shift toward greener conditions. For most reactions, this shift is underway or well advanced, and catalyst loadings have been decreased to below 1 mol ppm. An abundance of catalytic systems are now available, and it is sometimes difficult to identify the best one, because the substrates examined can vary widely from publication to publication. In the future, emphasis should be placed on the studying the full scope of the reaction at mol ppm catalyst loadings, rather than examining a few examples at these levels during the reaction‐optimization process. magnified image